Systems and methods for treating gastroesophageal reflux disease

ABSTRACT

Systems and methods for treating gastroesophageal reflux disease (GERD) includes minimally invasively implanting a stimulating device in a patient&#39;s esophagus in the region proximate the lower esophageal sphincter (LES). The patient is provided with a questionnaire related to his disease via an online service. The questionnaire is accessed on a mobile device, such as a cell phone, or on a computer with network access. The data from the sensors and the answers from the questionnaire are analyzed together by a health care provider using the online service. The data and answers are used to program the stimulating device, via the mobile device or computer, to optimize treatment.

CROSS REFERENCE

The present application is a continuation of U.S. patent applicationSer. No. 13/447,168, entitled “Systems and Methods for TreatingGastroesophageal Reflux Disease”, filed on Apr. 14, 2012, which, inturn, relies on U.S. Provisional Application No. 61/475,368, filed onApr. 14, 2011, entitled “Electrical Stimulation Systems and Methods”,which are incorporated herein by reference. The present application isalso a continuation in part of U.S. patent application Ser. No.13/041,063, entitled “Device and Implantation System for ElectricalStimulation of Biological Tissues”, filed on Mar. 4, 2011, now U.S. Pat.No. 8,712,529, issued on Apr. 29, 2014, which is also incorporatedherein by reference.

FIELD

This invention relates generally to a method and apparatus forelectrical stimulation of the biological systems. More particularly,this invention relates to methods and systems for treatinggastroesophageal reflux disease (GERD) by implanting an electricalstimulation device using laparoscopic or endoscopic techniques,capturing an eating event and detecting eating, using an implantableelectrical stimulation device, enabling a patient to interface with animplanted stimulation device, and applying predefined treatmentprocesses.

BACKGROUND

Gastro-esophageal reflux disease (GERD) is a common problem and isexpensive to manage in both primary and secondary care settings. Thiscondition results from exposure of esophageal mucosa to gastric acid andbile as the gastro-duodenal content refluxes from the stomach into theesophagus. The acid and bile damages the esophageal mucosa resulting inheartburn, ulcers, bleeding, and scarring, and long term complicationssuch as Barrett's esophagus (pre-cancerous esophageal lining) andadeno-cancer of the esophagus.

Lifestyle advice and antacid therapy are advocated as first linetreatment for the disease. However, since most patients with moderate tosevere cases of GERD do not respond adequately to these first-linemeasures and need further treatment, other alternatives includingpharmacological, endoscopic, and surgical treatments are employed.

The most commonly employed pharmacological treatment is daily use of H2receptor antagonists (H2RAs) or proton-pump inhibitors (PPIs) for acidsuppression. Since gastro-esophageal reflux disease usually relapsesonce drug therapy is discontinued, most patients with the disease,therefore, need long-term drug therapy. However, daily use of PPIs orH2RAs is not universally effective in the relief of GERD symptoms or asmaintenance therapy. Additionally, not all patients are comfortable withthe concept of having to take daily or intermittent medication for therest of their lives and many are interested in nonpharmacologicaloptions for managing their reflux disease.

Several endoscopic procedures for the treatment of GERD have been tried.These procedures can be divided into three approaches: endoscopicsuturing wherein stitches are inserted in the gastric cardia to plicateand strengthen the lower esophageal sphincter, endoscopic application ofenergy to the lower esophagus, and injection of bulking agents into themuscle layer of the distal esophagus. These procedures, however, are notwithout their risks, besides being technically demanding and involving along procedure time. As a result, these procedures have largely beendiscontinued.

Open surgical or laparoscopic fundoplication is also used to correct thecause of the disease. However, surgical procedures are associated withsignificant morbidity and small but not insignificant mortality rates.Moreover, long-term follow-up with patients treated by surgery suggeststhat many patients continue to need acid suppressive medication. Thereis also no convincing evidence that fundoplication reduces the risk ofesophageal adenocarcinoma in the long term.

While electrical stimulation has been suggested for use in the treatmentof GERD, an effective electrical stimulation system has yet to bedemonstrated. In particular, the prior art teaches that effectiveelectrical stimulation requires active, real-time sensing for apatient's swallow and, based on a sensed swallow, to immediately ceasestimulation. For example, certain prior art approaches require theconstant sensing of certain physiological changes in the esophagus, suchas changes in esophageal pH, to detect acid reflux and/or esophagealmotility and, based on such sensed changes, initiating or terminating anelectrical stimulation to instantaneously close or open the LES,respectively, thereby avoiding an acid reflux episode. Other prior artapproaches require continuous stimulation with sensing for swallow andstopping stimulation to allow for normal swallow to happen. This createsa complex device and has not proven to be feasible or effective inpractice.

Therefore, there is still a need for a safe and effective method oftreatment that can help alleviate symptoms of GERD in the long term,without adversely affecting the quality of life of the patients. Inparticular, there is a need for simple, efficient GERD device andtreatment methods that does not inhibit a patient from swallowing and donot rely on an instantaneous response from the patient's LES to avoidepisodes of acid reflux. There is a need for treatment protocols anddevices which are programmed to implement such protocols, which can beeasily programmed and do not require complex physiologic sensingmechanisms in order to operate effectively and safely. In addition,there is still a need for minimally invasive and effective treatment forobesity. Moreover, there is not only a need for better devices instimulation based therapies, but there is also a need for a safe andminimally invasive method and system that enables easy and expeditiousdeployment of such devices at any desired location in the body.

It is further desirable to have a system for the treatment of GERD whichincludes a stimulator and an optional sensor adapted to be placed in apatient's LES tissue.

It is further desirable to have a system for the treatment of GERD whichincludes an active implantable medical device (AIMD) and temporarysensor adapted to be placed in a patient's GI lumen where the sensorsare designed to naturally dissolve or pass out through the lumen and theAIMD is adapted to dynamically acquire, process, measure the quality of,and use sensed data only when the sensor is present.

It is further desirable to have a system for the temporary treatment ofGERD which includes an AIMD, which is adapted to be placed in apatient's GI lumen, designed to naturally dissolve or pass out throughthe lumen, and is adapted to deliver electrical stimulation to tissue ator in the vicinity of the LES. Such temporary stimulation scheme canadditionally be used for pre-screening of patients likely to benefitfrom permanent stimulation.

It would further be desirable for the stimulator to use periodic oroccasional sensing data to improve the treatment of GERD by dynamicallydetecting when a sensor is present, determining when a sensor istransmitting, or capable of transmitting, data, and processing thesensed data using an application having a special mode whichopportunistically uses the sensed data to change stimulation parameters.

It is also desirable to automate the setting or calibration of some orall device parameters in order to reduce the need for medical follow-upvisits, reduce burdens on healthcare providers and patients, decreasethe rate of programming mistakes, and improve outcomes, therebyimproving the treatment of GERD.

SUMMARY

The present specification is directed toward a device, having aplurality of dimensions, adapted for placement proximate a patient'slower esophageal sphincter (LES) using endoscopic or laparoscopic orsurgical techniques and programmed to treat esophageal dysfunction,comprising a stimulator enclosed within a housing and a plurality ofelectrodes wherein said electrodes are attached to the outer surface ofthe housing using conductors at least 1 mm in length. In one embodiment,the electrodes are adapted to be placed in a right or left anteriorquadrant of the LES. In one embodiment, the housing comprises a needlehaving a length in the range of 5-50 mm and, more preferably, in therange of 10-25 mm, for creating a pathway for electrode implantationinto the muscularis of the LES.

In one embodiment, electrodes are of sufficient length to allow them tobe placed entirely within the LES. In another embodiment, the electrodesare of sufficient length to allow them to be placed proximate to the LESwherein the electrical field generated stimulates the LES.

In one embodiment, the device is at least 6 mm long and no more than 10cm long to minimize fibrosis within peritoneal cavity.

In one embodiment, the device is adapted to be inserted into alaparoscopic trocar and has a diameter of greater than 6 mm but lessthan 25 mm.

In one embodiment, the device has an energy source that is rechargeable.In one embodiment, the device has a recharge frequency of no more thanonce per day for 6 hours. In one embodiment, the device has an energysource that is a battery that is a solid state battery, lithium ionbattery, or super capacitor battery. In another embodiment, the devicehas an energy receiving unit anchored to an abdominal wall of thepatient to maximize coupling between energy transmitting and receivingunits. In another embodiment, the is not rechargeable and has an implantlife of at least 1 year.

In one embodiment, the electrodes of the device are permanently attachedto the housing by insulated conductors no longer than 65 cm. In anotherembodiment, the electrodes of the device are attached to the housing byinsulated conductors which are detachable from the housing and are nolonger than 65 cm.

In one embodiment, the device is adapted to be attached to an abdominalwall of the patient. In another embodiment, the device is adapted to beattached to the outer surface or serosa of a stomach wall of thepatient.

In one embodiment, the device is adapted to be delivered and anchoredthrough a single port laparoscopic procedure. In another embodiment, thedevice is adapted to be delivered and anchored using an articulatedtrocar in a laparoscopic procedure. In yet another embodiment, thedevice is adapted to be delivered into a peritoneal cavity of thepatient through an incision that is created for a laparoscopic port.

The present specification is also directed toward a system for detectingeating by a patient, having a gastrointestinal tract, comprised of atransmitter and a receiver that communicate with each other, wherein thetransmitter is placed within a portion of the gastrointestinal tract,wherein the receiver is placed within a portion of the gastrointestinaltract, wherein the transmitter and receiver are separated by a portionof the gastrointestinal tract, and wherein a modulation of thecommunication between the transmitter and receiver is monitored by aprocessor and used by the processor to determine if the patient hasingested a quantity of liquid, solids, or both.

In various embodiments, the transmitter is adapted to be placed on aportion of an abdominal wall of the patient, a portion of an esophagusof the patient, a portion of a lower esophageal sphincter of thepatient, a portion of a cardia sphincter of the patient, or an outeranterior stomach wall of the patient.

In various embodiments, the receiver is adapted to be placed on aportion of an abdominal wall of the patient, a portion of an esophagusof the patient, a portion of a lower esophageal sphincter of thepatient, a portion of a cardia sphincter of the patient, or an outeranterior stomach wall of the patient.

In one embodiment, modulation occurs when a distance between thetransmitter and receiver is affected by an ingestion of liquid, food, orboth.

In one embodiment, the distance between the transmitter and receiver iscontinuously measured to determine if liquid, food, or both is beingingested. In various embodiments, the distance is measured usingultrasonic waves, electric fields, magnetic fields, optical waves, orelectro-magnetic fields.

The present specification is also directed toward a method for treatinggastroesophageal reflux occurring within a patient comprising implantingwithin the patient a stimulation device having a stimulator enclosedwithin a housing and a plurality of electrodes attached in electricalcommunication with said stimulator wherein said electrodes are anchoredin a position that is at least 1 mm and, more preferably, at least 5 mm,from the patient's cardiac tissue. In another embodiment, the electrodesare positioned at a distance at least ¼, and more preferably, greaterthan ½, the shortest distance between two electrodes, from the patient'scardiac tissue. In another embodiment, the electrodes are positionedsuch that the electric field is less than 75% of the maximum electricfield between two electrodes.

In one embodiment, the stimulator has a plurality of anchor points andanchoring is performed by sutures or Nitinol suturing techniques. Inanother embodiment, the stimulator has a plurality of fixation pointsand fixation is performed by a plurality of clips.

The present specification is also directed toward a method for treatinggastroesophageal reflux occurring within a patient comprising implantingwithin the patient a stimulation device having a stimulator enclosedwithin a housing and a plurality of electrodes attached in electricalcommunication with said stimulator wherein said electrodes are anchoredin a position that is at least 1 mm and, more preferably, at least 5 mm,from the patient's main vagal trunk.

In one embodiment, the stimulator has a plurality of anchor points andanchoring is performed by sutures or Nitinol suturing techniques. Inanother embodiment, the stimulator has a plurality of fixation pointsand fixation is performed by a plurality of clips.

The present specification is also directed toward a method of treatinggastroesophageal reflux disease (GERD) in a patient having a loweresophageal sphincter (LES) comprising: implanting a stimulation deviceproximate the LES wherein the stimulation device is programmable andprovides electrical stimulation to the LES to produce a contraction ofthe LES; measuring a pH in the patient's esophagus and generating pHdata; transmitting the pH data to a processor housed within a computingdevice external to the patient and storing the pH data within thecomputing device; electronically presenting the patient with questionsrelating to symptoms arising from the patient's GERD; electronicallyreceiving answers from the patient; analyzing the pH data in relation tothe answers to generate programming parameters; and programming thestimulation device using the programming parameters.

In one embodiment, measuring the pH comprises implanting at least one pHsensor in the esophagus proximate the LES wherein the pH sensor isconfigured to continually monitor the pH of the lower esophagus and iscapable of transmitting sensed pH data. In one embodiment, the pH sensoris adapted to be implanted endoscopically.

In various embodiments, the questions include any one or more ofquestions relating to a timing of the patient's GERD symptoms, aduration of the patient's GERD symptoms, a severity of the patient'sGERD symptoms, the patient's meal times, types of food ingested by thepatient, types of liquid ingested by the patient, the patient's sleeptimes, and the patient's exercise regimens.

In one embodiment, programming of the stimulation device compriseschanging at least one operational parameter, wherein the at least oneoperational parameter comprises stimulation start time, stimulationduration, and/or stimulation amplitude.

In one embodiment, the questions are electronically presented to thepatient by communicating those questions through a network to acomputing device in the patient's possession. In one embodiment, thecomputing device is a mobile phone.

In one embodiment, the pH data, programming parameters, and patient'sanswers are stored in a memory and in relation to a user account that iscontrolled by the patient and accessible using a network accessiblecomputing device.

In one embodiment, the method of treating gastroesophageal refluxdisease (GERD) in a patient having a lower esophageal sphincter (LES)further comprises providing an online service that electronicallyreceives the pH data through a network and stores the pH data. In oneembodiment, the online service electronically receives the patient'sanswers through the network and stores the answers. In one embodiment,the online service also electronically receives other data representingat least one physiological value wherein the physiological valueincludes at least one patient eating state, supine position, level ofphysical activity, or blood glucose level.

In one embodiment, the method of treating gastroesophageal refluxdisease (GERD) in a patient having a lower esophageal sphincter (LES)further comprises using a remote process to automatically program thestimulating device after generating the programming parameters.

In one embodiment, the online service further electronically transmitsreminders and/or recommendations to the patient regarding diet andexercise regimens. In one embodiment, the online service furtherelectronically receives questions and appointment requests from thepatient.

In one embodiment, the online service monitors the patient's compliancewith at least one of a treatment, diet, or exercise regimen or scheduledappointment, determines a degree of compliance, and generates a rewardfor the patient based on the degree of compliance.

The aforementioned and other embodiments of the present invention shallbe described in greater depth in the drawings and detailed descriptionprovided below.

DESCRIPTION OF THE DRAWINGS

The aforementioned and other embodiments shall be described in greaterdepth in the drawings and detailed description provided below.

FIG. 1 is a first exemplary esophageal pH trace of a patient receivingnon-specific LES electrical stimulation;

FIG. 2 is a second exemplary esophageal pH trace of the same patientreceiving LES electrical stimulation therapy following the implantationof a patient specific optimization;

FIG. 3 is a flowchart detailing one process for optimizing theoperational parameters of a patient device; and,

FIG. 4 is a flowchart detailing another process for optimizing theoperational parameters of a patient device.

DETAILED DESCRIPTION

The present specification describes methods and systems for treatinggastroesophageal reflux disease (GERD) by implanting an electricalstimulation device using laparoscopic or endoscopic techniques,capturing an eating event and detecting eating, using an implantableelectrical stimulation device, enabling a patient to interface with animplanted stimulation device, and applying treatment processes. Itshould be appreciated that the methods and systems are being describedwith respect to specific embodiments, but are not limited thereto.

The present specification is directed towards multiple embodiments. Thefollowing disclosure is provided in order to enable a person havingordinary skill in the art to practice the claimed embodiments. Languageused in this specification should not be interpreted as a generaldisavowal of any one specific embodiment or used to limit the claimsbeyond the meaning of the terms used therein. The general principlesdefined herein may be applied to other embodiments and applicationswithout departing from the spirit and scope of the claimed embodiments.Also, the terminology and phraseology used is for the purpose ofdescribing exemplary embodiments and should not be considered limiting.Thus, the present specification is to be accorded the widest scopeencompassing numerous alternatives, modifications and equivalentsconsistent with the principles and features disclosed. For purpose ofclarity, details relating to technical material that are known in thetechnical fields related to the claims have not been described in detailso as not to unnecessarily obscure the claimed embodiments.

It should be appreciated that the systems and methods described hereincan be used with a plurality of different devices, including thoseelectrical stimulation devices disclosed in U.S. Pat. No. 7,702,395,U.S. patent application Ser. Nos. 10/557,362 and 12/598,871, U.S. Pat.No. 6,901,295, PCT Application No. PCT/US08/56479, U.S. patentapplication Ser. Nos. 12/030,222, 11/539,645, 12/359,317, and13/041,063, and PCT Application Numbers PCT/US09/55594 andPCT/US10/35753, which are herein incorporated by reference.

Devices Adapted to Be Implanted Using Laparoscopic Surgical Techniques

In one embodiment, surgical or endoscopic techniques are used to implantan electrical stimulation device to treat GERD in a manner that is lessinvasive than those currently employed.

In one embodiment, an electrical stimulation device, or portionsthereof, is adapted to be placed within or proximate the loweresophageal sphincter using laparoscopic surgical techniques andprogrammed to treat GERD, diurnal GERD, nocturnal GERD, and/or transientlower esophageal sphincter relaxation (tLESR). The outer surface of thedevice has electrodes attached thereto which comprise conductors atleast 1 mm in length. The device may be a conventional pulse generator,a miniature pulse generator, or a microstimulator.

In one embodiment, the electrodes are adapted to be placed in the rightanterior quadrant of the LES. In one embodiment, the electrodes areadapted to be placed the furthest possible distance from cardiac tissuewhile still being positioned to stimulate the LES. In one embodiment,the electrodes are positioned at least 1 mm and, more preferably, atleast 5 mm from the patient's cardiac tissue. In another embodiment, theelectrodes are positioned at a distance at least ¼, and more preferably,greater than ½ the shortest distance between two electrodes, from thepatient's cardiac tissue. In another embodiment, the electrodes arepositioned such that the electric field is less than 75% of the maximumelectric field between two electrodes.

In one embodiment, the device has a plurality of structures or memberswhich serve to anchor the device in the patient's tissue whereby thestructures or members are configured to enable anchoring using suturesor nitinol suturing techniques.

In one embodiment, the device has a plurality of fixation points,structures, or members which serve to fix the device in the patient'stissue, preferably using clips.

In one embodiment, the device has at least one protrusion or needle forforming a pathway through a patient's tissue, where the pathway servesto enable electrode implantation into the muscularis of the patient'sLES. In various embodiments, the protrusion or needle measures from10-25 mm in length.

In one embodiment, the device comprises at least one electrode ofsufficient length that allows the electrode to be placed entirely withinthe LES, without extending beyond the LES.

In one embodiment, the device is at least 1 cm long and no more than 10cm long to minimize fibrosis within the peritoneal cavity.

In one embodiment, the device has a form factor, and is containedentirely within a housing, that can be inserted into a conventionallaparoscopic trocar. The device has dimensions greater than 6 mm, butless than 25 mm, in diameter. In another embodiment, the device isphysically configured and/or adapted to be delivered and anchoredthrough a single port laparoscopic procedure. In another embodiment, thedevice is physically configured and/or adapted to be delivered andanchored using an articulated trocar in a laparoscopic procedure. Inanother embodiment, the device is physically configured and/or adaptedto be delivered and anchored into the peritoneal cavity through anincision that is created and/or sized for a laparoscopic port.

In one embodiment, the device has a local energy source, such as abattery, that has one or more of the following characteristics: theenergy source is rechargeable; has a recharge frequency of once per dayfor 6 hours, once per week for approximately 60 minutes, once per month,or once per year, comprises lithium ion battery technology, comprisessolid state battery technology, comprises lithium polymer batterytechnology, comprises super capacitor technology; is not rechargeable,is not rechargeable and/or has an implant life of at least one year.

In one embodiment, the device comprises an energy receiving unit that isadapted to be anchored into the abdominal wall in order to maximizecoupling between an energy transmitting unit and an energy receivingunit.

In one embodiment, the device has electrodes which are permanentlyattached by insulated conductors. In another embodiment, the electrodesattached to insulated conductors are detachable from the device.

In one embodiment, the device is adapted to be attached to the abdominalwall, on either the subcutaneous side or the peritoneal side, and/oradapted to be attached to the submucosa or outer surface or serosa ofthe stomach wall.

In one embodiment, the device is physically configured or adapted to beplaced entirely within the submucosa adjacent to the LES.

In one embodiment, the device is adapted to be implanted within apatient such that the device is oriented between 45 degrees and 135degrees within a standing patient in relation to a ground surface, whichis at 0 degrees.

In one embodiment, the device comprises a plurality of electrodes whichare adapted to be implanted such that they face the same LES muscularis.

Eating Detection Systems

In one embodiment, the present system is used to detect an eating eventbased upon an implanted transmitter and an implanted receiver, which areseparated by a distance in a range of 0.5 cm to 20 cm, or preferably 1-2cm. In one embodiment, the system comprises an implantable transmitterand receiver pair which are used to determine if a patient has ingesteda quantity of liquid, solids, or both.

In one embodiment, the transmitter is adapted to be placed in or on theabdominal wall. In one embodiment, the transmitter is adapted to beplaced on the outer anterior stomach wall, to be placed on the serosalsurface of the stomach, to cross the LES, to cross the esophagus, orcross the cardia sphincter.

In one embodiment, the receiver is adapted to be placed in or on theabdominal wall. In one embodiment, the receiver is adapted to be placedon the outer anterior stomach wall.

In one embodiment, the transmitter and receiver are placed such that thedistance between the transmitter and receiver is only modulated,changed, or otherwise affected by ingested liquid, food, or both. Acontroller monitors the distance between the transmitter and receiver.As the distance changes, the controller determines whether the distancechange is indicative of whether a patient has ingested liquid, food, orboth. In one embodiment, the distance between the transmitter andreceiver is continuously measured to determine if liquid, food, or bothis continuously being ingested. In one embodiment, the distance betweenthe transmitter and receiver is continuously measured to differentiateif liquid, food, or both has been ingested.

The distance between the transmitter and receiver pair may be measuredusing ultrasonic sensors, electric field sensors, magnetic fieldsensors, electro-magnetic field sensors, and/or optical sensors.

Patient Interfacing Systems

In one embodiment, the system is adapted to be used to treat GERD usingtreatment algorithms and systems for collecting patient data, which areused to optimize treatment efficacy.

In one embodiment, the specification provides apparatuses and methodsfor collecting diet or lifestyle data from patients that are related toand are used to evaluate reflux events and/or GERD symptoms. Such datacan be, for example, meal times, the type of food ingested, the type ofliquid ingested, exercise regimens, sleep routines, as well as datarelated to time and severity of reflux symptoms.

The specification describes an apparatus used for said lifestyle datacollection as well as storage and communication of said data. In oneembodiment, the apparatus takes the form of a stand-alone devicespecially designed for this purpose. In another embodiment, theapparatus is an embedded component of a system used for health relatedpurposes within the patient, such as a charger for an implantable devicethat includes lifestyle data collection and communication capabilities.In another embodiment, the apparatus includes software running ongeneral purpose systems such as computers, smartphones, or other mobiledevices. The device can be battery operated, portable, and handheld orhave a desktop form factor using mains power. In another embodiment,such data is collected using paper diary and input into the externaldevice by a health care professional and inputted into the device usingwireless communication.

In one embodiment, the device performs multiple functions to enable thetreatment of patients. For example, the device is adapted to be used forwireless charging of an implantable pulse generator (IPG) battery usedas an energy source for an electrical stimulator for the LES. In anotherembodiment, the device can be integrated into a physician controlledcomputing device which is used in a clinic to wirelessly program thedevice parameters and which may also be used to collect patient input.Another example is that of a diagnostic pH monitoring device adapted toreceive patient lifestyle data. Various combinations of the devicesmentioned can be implemented and be interconnected using wireless orwired communication so that patient data is available when decisions aretaken on parameter setting of the stimulation device.

In another embodiment, the device is programmable to implement changesin GERD treatment algorithms based on any patient data collected.

One objective of the device is to treat, prevent, or otherwise minimizeinappropriate relaxations of the LES while allowing appropriaterelaxations of the LES, such as for vomits, swallows, or burps. Anotherobjective of the device is to stimulate the LES while not inhibitingnormal physiological relaxations of the LES, such as for vomits,swallows, or burps. Another objective of the device is to reduce apatient's esophageal pH and/or modulate a patient's LES pressure whilenot causing a patient's cardia sphincter to completely close.

In some embodiments of the present specification, an apparatus forcombining data from implantable sensors with patient input is used foroptimizing GERD treatment algorithms. Preferably, a sensor generates asignal indicative of the swallowing of food and/or content thereof,providing information related to eating habits of the patient. Ananalysis module typically determines a quality of the food, for example,whether it is predominantly solid or liquid, and stores this informationin an electronic memory. Alternatively or additionally, the analysismodule determines other characteristics of the ingested material, forexample, the nutritional, chemical, and/or caloric content. “Food,” asused in the context of the present patent application and in the claims,is to be understood as including a bolus of solid food, a liquid, orboth a solid food bolus and a liquid. “Swallowing,” as used in thecontext of the present patent application and in the claims, is to beunderstood as being indicative of the onset of eating as defined by thecontraction of musculature of the esophageal body and relaxation of theLES to pass food from the esophagus into the stomach.

In some embodiments of the present invention, swallowing is detected bytracking the electrical activity in muscle tissue in the stomach, in theesophagus or in other parts of the GI tract. Typically, the commencementof enhanced electrical activity is also detected in muscle tissue in thestomach. Measurement of the time delay between swallowing and thecommencement of electrical activity in the antrum is typically used todifferentiate between solid and liquid matter, which are generallypassed at different rates through the stomach.

Alternatively or additionally, swallowing is detected by at least onesensor placed at a site on the gastrointestinal tract wherein the sensorgenerates a signal indicative of swallowing. Appropriate sites include,but are not limited to, a site on the esophagus, a site on the stomach,and a site on the throat.

Whenever detection of swallowing is described in the present patentapplication with respect to any specific sensor such as a sensor in theLES, it is to be understood as being by way of example, and not asexcluding, detection by a sensor located elsewhere on thegastrointestinal tract.

Typically, electrical activity response criteria of the stomach of anindividual patient are determined and calibrated by measuring theresponse of the patient's stomach to various types of solid and liquidfood. To ensure appropriate compliance, calibration is typicallyperformed under the supervision of a healthcare worker.

For some applications, various supplemental sensors are also applied tothe gastrointestinal tract or elsewhere on or in the patient's body.These supplemental sensors, which may comprise pH sensors, blood sugarsensors, ultrasound transducers or mechanical sensors, typically conveysignals to a control unit of the apparatus indicative of acharacteristic of solids or liquids ingested by the patient. Forexample, an ultrasound transducer may be coupled to indicate whetheringesta are solid or liquid, and a pH sensor may indicate that an acidicdrink such as tomato juice was consumed rather than a more basic liquidsuch as milk.

In some embodiments, the data collected from the patient is used toadjust the parameters of electrical stimulation applied to the loweresophageal sphincter with the intent of enhancing its tone using animplantable neuro-stimulating system.

In such applications the electrical stimulation is optimally deliveredintermittently rather than continuously. Such intermittent stimulationis beneficial to preserve battery life of the implantable device andalso to minimize the risk of physiological adaptation to the electricalstimulation that might reduce its efficacy over time or requireincreasing levels of energy to be delivered.

In another embodiment, the sensor is a pH sensor that records the pHdata indicative of a reflux event and such data is used to design astimulation algorithm to treat GERD. In this embodiment the stimulationcould be programmed to be delivered a fixed time prior to such measuredevent to prevent future reflux events.

Adjusting Stimulation Time Based on Meal Times and Related Symptoms

In many GERD patients, there is significant association between foodintake and symptoms. In some embodiments, the stimulation timing isadjusted manually or automatically to meal times so as to optimizeefficacy of electrical stimulation of the LES in treating GERD.

Additionally, treatment algorithms take into account the uniqueassociation between stimulation session timing and the enhancementeffect on the tone of the LES. Two important elements of this effect arecritical in setting stimulation timing: latency effect and residualeffect.

The latency effect means that the impact on tone is not immediate uponinitiation of electrical stimulation but rather some time delay,typically between 5 minutes and one hour, needs to pass before the tonereaches optimal enhancement. In addition, the electrical stimulation isknown to have a residual effect beyond the time of cessation ofstimulation that typically lasts between 20 minutes and 6 hours but canlast up to 24 hours. All of the above means that initiation of thestimulation session needs to start enough time before any potential mealtime in order to “cover” the expected reflux events or symptomsfollowing the meal.

In order to tailor the stimulation time to eating habits of differentpatients and to the changes of eating habits of each patient over time,some embodiments use patient input and/or data from physiologicalsensors.

Utilization of Patient Input

In a preferred embodiment the patient input data includes answers to thefollowing exemplary questions:

1. At what times do you start your three most important meals of the day(three can vary from 1-8)

2. When you have GERD symptoms, do they usually—mark one answer:

-   -   (a) follow meals?    -   (b) happen during night time or when you lay down?    -   (c) occur both when you lay down and after meals?    -   (d) occur at a specific time of the day unrelated to meals or        body position?

3. What times of day do you typically feel reflux symptoms (allow 2-6answers)?

The answers to the above questions can typically be used as follows: Ifthe answer to Q2 is (a) or (c), then specific stimulation sessions areprogrammed to start prior to, or in proximity to, the start of mealsassociated with symptoms. Setting the timing of stimulation to theearliest reported start of the meal is beneficial because of the knownlatency effect of electrical stimulation on LES tone. The latency periodis between about 15 minutes to one hour so a preferred embodiment willprogram stimulation session to start one hour before the earliestreported time of meal start.

Answers to the questions above should be preferably obtained before thefirst time stimulation parameters are set and then be verifiedoccasionally or as patients habit change.

An exemplary stimulation algorithm may include sessions 30 minutesbefore each meal, when a supine position is detected and specific timesprior to reported GERD events. However, in a patient with erraticlifestyles, the total number of daily sessions can be equally spacedduring the day such as every 2 hours or every 4 hours. In anotherembodiment, based on predominant upright reflux or predominant supinereflux, more sessions could be programmed for the upright or supineperiod, respectively.

Utilization of pH Input in Conjunction with Patient Input

In a preferred embodiment, acid exposure traces (pH esophageal traces)from the subject are also used in conjunction with the meal diary of thesubject, if available, to determine optimal treatment. Such traces areused as follows:

1. Meal times indicated on the pH traces are used in combination withmeal periods reported by the patient on the patient communicationsystem. Such combination can be performed so that meal times from bothsources are super-imposed and the combined set of meal times is used inthe same way as a patient diary to adjust stimulation times.

2. Acid exposure events are analyzed so that time relations to variouspatient conditions (as indicated on the pH trace) are noted. Suchconditions can be meal times, supine position and reported symptoms.

In a preferred embodiment, the acid exposure events are used indifferent stages of the patient treatment cycle to optimize treatment asfollows:

During the pre-treatment stage, acid exposure times indicate if thepatient has a tendency to reflux following meals, during sleep or both,serving as a validation to the patient questionnaire as described. Suchvalidation is used in some embodiments to adjust parameters so that ifat least one of the following conditions is fulfilled, then supinestimulation is programmed in the IPG: (a) patient questionnaire reportssupine symptoms (b) in more than 0-5% of supine time acid exposure isnoted in the pH trace or (c) any esophageal pH event is associated withpatient symptom.

During the patient treatment stage, if a patient reports GERD symptoms,sub-optimal improvement in GERD and/or symptoms appearing in specifictimes, then the questionnaire is repeated and parameters adapted asnecessary. The pH traces indicate times during which treatment is notoptimal and therefore an enhanced stimulation regime is required. The pHtraces are further used to prescribe the said treatment enhancementwhere as acid exposure events are first related to patient reports orother external information such as meal times, supine time, exercisetime etc. and a stimulation session is added about one hour prior to theexpected acid exposure event or preferably adjustable between 5 minutesand two hours before an expected reflux event. The pH trace can berelated to the patient questionnaire in the following way: If an acidevent is detected at a certain time and a meal is indicated about 0-2hours prior to that event, then the patient is asked about the earliesttime that such a meal is typically started so that the enhancedtreatment addresses not only the events of the specific day of the testbut also the variable meal times that the patient reports.

An example of using a combination of patient reports and pH traces fortreating a patient is described. The patient is a GERD patient thatpresented with high acid exposure and GERD symptoms prior to treatment.The patient was implanted with an IPG that was programmed to deliverstimulation irrespective of patient meal times and symptom times of acidexposure periods. During the first two weeks of treatment, the patientreceived a stimulation session at 2 pm, at the time at which the devicedetected sleep (using an accelerometer that sensed when the patient haddecreased motion and was in a supine posture for at least 30 minutes),and 8 hours following the sleep detection using the above algorithm.

Following two weeks of treatment, the patient was still complaining ofGERD symptoms with only a small improvement compared to baseline. Atweek 2, the patient was questioned about eating habits and his pH tracewas reviewed so as to adjust the stimulation times. The patient wasreporting meals at about 2 pm, which was verified in his baseline pHtrace. The pH trace also showed a short meal at 4:30 pm. The patientalso complained of symptoms between 5 and 6 pm so a 4 pm stimulationsession was added. Finally, a 6 pm stimulation was added to address postdinner symptoms. At week 4, the patient was questioned again aboutsymptoms and this time a dramatic improvement was noted. The pH exposuretrace on the current stimulation algorithm confirmed an improvement ornormalization of esophageal acid exposure.

Additional patients underwent similar processes with similar results,demonstrating the importance of tailoring stimulation time to precedemeals and other events that are precursors of pH exposure and GERDsymptoms.

Referring to FIG. 1 , an esophageal pH trace of the patient is shownwherein the shaded periods 105 indicate meal times and wherein areaswith esophageal pH<4 are considered abnormal acid exposure periods 110.The X-axis is time of day and the Y-axis is the pH at each given time.As shown, the patient presents with many events of acid exposure mainlypost meals (e.g. post 11 am breakfast 110 a, post 1-2 pm lunch 110 b andpost 9:30 pm dinner 110 c) as well as during night time (supine time 115marked as time between about 1 am and 8:30 am). Total acid exposure is10.4% of the time, which is considered abnormal (4% is the threshold fornormal exposure). Such high acid exposure can result in various issuessuch as GERD symptoms, esophagitis, or Barrett's esophagus.

Referring to FIG. 2 , an esophageal pH trace of the patient is shownafter the patient, whose trace is shown in FIG. 1 , has been treatedwith electrical stimulation using the patient specific algorithm for 4weeks. The trace demonstrates that the majority of the esophageal acidexposure periods 210 are prevented and the esophagus acid exposuredecreased to only 3.6% of the recording time, which is considerednormal.

Methods and Utilities Related to a Patient Communication Device

The following will describe a new component of the GERD treatment thatcan utilize patient input, communicate with the implantable pulsegenerator (IPG) and/or communicate externally with a clinic or otherservice provider. Such an apparatus, namely a “patient communicationdevice”, can preferably include a processing unit that can integrate andanalyze patient input with or without additional data as describedabove, such as pH data, and integrate the data to form a treatmentrecommendation in the form of stimulation session times, amplitudes,duration, etc. The patient communication device operates via an onlineservice in which a patient can access his key physiological data andanswer questions, such as those on the patient questionnaire that willhelp existing or new doctors program the patient's IPG. Use of thepatient communication device frees the patient from being tied to oneparticular doctor and prevents the patient from being in a situationwhere they need treatment adjustment but don't have access to theirdata.

In one embodiment, any computer running the appropriate software andhaving online access can function as a patient communication device.Additionally or alternatively, the patient communication device can be asmart phone or other mobile device running the software so that thepatient can use it without a need for a computer.

FIGS. 3 and 4 are flowcharts describing exemplary embodiments ofdifferent methods by which the online service and patient communicationdevice operate to tailor GERD therapy for a specific patient. At steps302 and 402, the patient communication device acquires sensedphysiological data from sensors within the patient and, in steps 304 and404, stores the data online using cloud based storage. The stored datais reviewed by a processor at steps 306 and 406 or a health careprovider in a clinic or hospital setting at steps 308 and 408. Invarious embodiments, the sensed physiological data includes any one ormore of esophageal pH, stomach pH, ingestion of food (using distancesensors as described above), supine position, patient weight, patientphysical activity, and blood glucose level.

Using the sensed physiological data as a basis, either the remoteprocessor at steps 310 and 410 or the health care provider at steps 312and 412, generates a set of questions designed to further modify theGERD therapy. In various embodiments, the questions include any one ormore of those in the questionnaire and questions regarding timing ofreflux symptoms, duration of reflux symptoms, intensity of refluxsymptoms, meal times, types of food ingested, types of liquid ingested,sleep times, and exercise regimens. At steps 314 and 414, the onlineservice transmits the question set to the patient communication devicewhich then presents it to the patient. At steps 316 and 416, the patientanswer the questions directly on the patient communication device andthe answers are stored in the cloud based storage at steps 318 and 418.The answers are also reviewable by a remote processor or a health careprovider in a clinic or hospital setting.

In one embodiment, as shown at step 320 in FIG. 3 , a processor locatedat the clinic or hospital automatically compares the sensedphysiological data and the patient's answers and at step 324automatically generates a set of operational parameters for the IPGspecific to the patient's data. In another embodiment, as shown at step322, a health care provider reviews the data and patient answers andthen at step 326 programs operational parameters for the IPG. In anotherembodiment, as shown in step 420 in FIG. 4 , a processor is locatedwithin the patient communication device automatically compares thesensed physiological data and the patient's answers and at step 424automatically generates a set of operational parameters for the IPGspecific to the patient's data. In yet another embodiment, as shown atstep 422, the patient compares the data and his answers and at step 426programs the IPG using the patient communication device. In variousembodiments, the operational parameters include any one or more ofstimulation start times, stimulation duration, and stimulationamplitude.

The generated or programmed operational parameters are then transmittedto the IPG. When the operational parameters are generated remotely by aprocessor or programmed remotely by a health care provider, saidparameters are transmitted by the online service to the patientcommunication device at step 328, which then transmits the parameters tothe IPG at step 330. When the operational parameters are generatedlocally by a processor on the patient communication device or areprogrammed by the patient using the patient communication device, thenthe patient communication device transmits said parameters directly tothe IPG at step 428.

In a preferred embodiment, the patient questionnaire is applied using apatient communication device, being convenient for the patient as wellas facilitating electronic data collection and analysis. Accessing thequestionnaire is done via a web page to which patients log-on with acode from anywhere and the data will be transferred to the treatingclinic electronically through an electronic database utilizing cloudbased storage that is accessible by the clinic. In one embodiment,information relating to the patient, including the pH data, programmingparameters, and patient's answers, is stored in the memory and inrelation to a user account that is controlled by the patient andaccessible using a network accessible computing device. Patient datawill be protected from unauthorized access by standard web siteprotection tools such as SSL/HTTPS.

In a preferred embodiment, the clinic can communicate with the patientthrough the patient communication device. There can be various uses forsuch a communication channel, such as patient periodic remindersadvising him/her to log in and answer the questionnaire. The means ofcommunications can be standard, such as emails or instant phonemessages, or can use special software and/or communication interfaces.When the patient uses a mobile application, the entire communicationbetween the patient and the clinic can take place through the mobileapplication including patient reminders, questionnaire answering anddata transfer to the clinic. The clinic can use the application or theother communication channels used for patient reminders to send himother relevant material such as medication information, scheduling ofthe next clinic visit, diet recommendations, and advice on variousproducts and services that can be determined based on the patientprofile stored in the clinic whereas such profile can be adapted fromtime to time based on the data communicated by the patient. The patientcommunication channel can be used for collecting additional medicalinformation from the patient that can be used as initial screeninginformation and may trigger (possibly in conjunction with physicianreview) scheduling in-person visits and specific tests.

In another preferred embodiment, the patient communication device can becentered around a patient charger that is used by the patient towirelessly charge an implantable IPG with a rechargeable battery. Such acharger can have a screen for displaying patient messages and a keyboardfor keying in information by the patient. It can also serve as a waystation that can have a communication channel (wireless or wired) with acell phone or a computer connected to the web to serve as a userinterface, communication channel or both.

In embodiments in which the patient communication device can alsoestablish a communication channel with the IPG, it can be adapted toconfigure or adjust the stimulation parameters to treat GERD of thesubject. The patient communication device is adapted to monitor, usingthe received data, information regarding the applied stimulation, theinformation selected from the group consisting of: an amount of time perday that the implantable control unit drives the stimulator to apply thestimulation to the GI tract, and a number of times per day that theimplantable control unit drives the stimulator to apply the stimulationto the patient and the time of day thereof.

For some applications, the patient communication system includes anoutput element, which is adapted to output the information regarding theapplied stimulation. In a preferred embodiment, the GI tract includesthe lower esophageal sphincter (LES) of the subject, and the one or moresensors are adapted to generate the respective sensor signalsresponsively to the GI tract physiological parameter of the esophagusand/or LES. For some applications, the patient communication device isadapted to monitor changes in the electrical properties of theesophageal tissue indicative of swallowing and/or the content of eachswallow. Such electrical properties can include, for example, sensing ofelectrical action potentials and/or changes in the tissue impedance. Insome embodiments, a gastric slow wave rate of the subject can be used asindicative of digestive state to improve the analytical capabilities ofthe system.

In one embodiment, the IPG is adapted to store data using patient input.The data is recorded using the accelerometer in the IPG. The patient cancommunicate the information to the IPG by simply tapping on the IPG andthe tapping is recorded by the accelerometer. In this embodiment, thenumber or intensity of taps could represent a specific event. Forexample, one tap on the device may indicate start of a meal event, whiletwo taps may indicate start of a reflux event. The event data can berecorded for download by the clinic to modify the stimulation algorithmor can be used by the IPG directly to modify the stimulation algorithmwithout input of a health care provider. The information gathered by theIPG will continuously modify the patient's lifestyle and GERD profileand adjust the stimulation algorithm to address the changing patientprofile.

In another embodiment, an external device is used which produces avibration with a characteristic that is specific to the event. Thepatient will place this device on the site of the IPG implant and pressa specific event button on the external device which will then vibratewith the characteristic specific to the event. The vibrations aretransmitted through the human tissue to the IPG which registers thespecific event. The event data can be recorded for download by theclinic to modify the stimulation algorithm or can be used by the IPGdirectly to modify the stimulation algorithm without input of a healthcare provider. The information gathered by the IPG will continuouslymodify the patient's lifestyle and GERD profile and adjust thestimulation algorithm to address the changing patient profile.

In another embodiment, the IPG is adapted to store information regardingeating habits of the subject as detected by the swallowing sensors. Forsome applications, the IPG includes an output element, which is adaptedto output the eating habit information. For some applications, thepatient communication device is adapted to integrate and verify patientanswers to the questionnaires with the eating detection data receivedfrom the IPG. The patient communication device can be adapted totransmit the integrated eating habit information to the clinic via thecommunication channel.

For some applications, the patient communication device is adapted toreceive, analyze and integrate indication of non-GI tract physiologicalparameters. Such parameters can include an indication of a weight of thesubject, level of physical activity of the patient, blood glucose of thepatient, etc. The patient communication device can generate a message tothe IPG for adjustment of parameters and/or a transmission of theinformation to the clinic.

For some applications, the IPG is adapted to modify a parameter of thestimulation at least in part responsively to the information. Forexample, the stimulation parameter may include an intensity of thestimulation, and the IPG is adapted to modify the intensity of thestimulation at least in part responsively to the information, and/or thestimulation parameter may include a timing parameter of the stimulation,and the IPG is adapted to modify the timing parameter of the stimulationat least in part responsively to the information.

In an embodiment, the patient communication device is adapted to becoupled to a remote service provider. In one embodiment, the remoteservice provider can analyze the patient data, for example, pH andsymptom data, and convert it into parameter setting changes recommendedfor a given patient, thereby making the work of the clinic easier andshorter. For some applications, the apparatus includes an externalcradle, and the patient communication device is adapted to be removablycoupled to the cradle, and to be coupled to the service provider via thecradle. For some applications, the patient communication device isadapted to receive information from the service provider. Alternativelyor additionally, the patient communication device is adapted to sendinformation to the service provider selected from the group consistingof at least a portion of the received data and information derived froman analysis of at least a portion of the received data.

In an embodiment, the patient communication device is configured toserve as a charger for the IPG. In such a case, the patientcommunication device includes a power source, and is adapted to drivethe power source to wirelessly transfer energy via one or moretransducers, and the implantable pulse generator includes a rechargeablebattery, and is adapted to receive the transmitted energy, using one ormore transducers, and charge the battery using the energy.

In one embodiment, the patient communication device is adapted to belocated remotely from the subject. In such an embodiment, the patientcommunication device is not capable of recharging the IPG. Data istransmitted between the patient communication device and the IPG via RFcommunication at a distance of up to 3 meters. In another embodiment,the patient communication device is adapted to be located proximate thesubject.

In another embodiment, the patient communication device is adapted to becoupled wired or wirelessly to a point-of-sale terminal. In oneembodiment, the online service monitors the patient's compliance withthe recommended treatment, diet, or exercise regimen or scheduledappointment, determines a degree of compliance, and generates a rewardfor the patient based on the degree of compliance. In an embodiment,generating the reward includes providing a financial incentive to thepatient. In one embodiment, providing the financial incentive is basedon a measure of successful responses to the clinic communicationrequests. In various embodiments, the financial incentive comprises anyone or more of the following: refunding to the patient a portion of thepurchase price of the device/and or software; providing a discount tothe patient on routine medical care; and, providing a free devicecharging session for rechargeable devices.

For some applications, a method includes sending a reminder from theservice provider to the site, and communicating the reminder to thesubject. In an embodiment, the method includes analyzing, at the serviceprovider, the eating-related information. For some applications,analyzing the eating-related information includes developing arecommendation based on the eating-related information, sending therecommendation from the service provider to the site, and communicatingthe recommendation to the subject from the site. For example, therecommendation may be selected from the group consisting of arecommended food and a recommended recipe. For some applications, therecommendation is commercial in nature.

For some applications, receiving of data from the IPG includes loggingthe data, and providing the financial incentive includes providing thefinancial incentive responsively to the logged data.

In an embodiment, providing the financial incentive includes providingthe financial incentive in response to determining, responsively to thedata, that the subject has followed a prescribed regimen. For someapplications, the regimen includes a diet regimen intended to improveGERD symptoms, and providing the financial incentive includes providingthe financial incentive upon determining, responsively to the data, thatthe subject has adhered to the prescribed diet regimen. Alternatively oradditionally, the regimen includes an exercise regimen, and providingthe financial incentive includes providing the financial incentive upondetermining, responsively to the data, that the subject has adhered tothe prescribed exercise regimen.

For some applications, functionality described herein with respect to apatient communication device is embodied that can communicate with astationary or portable receiving device located in the clinic and isconfigured to collect data from the patient communication system.

The above examples are merely illustrative of the many applications ofthe system of the present invention. Although only a few embodiments ofthe present invention have been described herein, it should beunderstood that the present invention might be embodied in many otherspecific forms without departing from the spirit or scope of theinvention. Therefore, the present examples and embodiments are to beconsidered as illustrative and not restrictive, and the invention may bemodified within the scope of the appended claims.

We claim:
 1. A system for treating a gastrointestinal condition of apatient, comprising: at least one electrode adapted to be implanted suchthat said electrode is configured to be in electrical communication witha lower esophageal sphincter (LES) of the patient to deliver a pulsestream in accordance with a plurality of stimulation parameters; a pulsegenerator in electrical communication with the at least one electrode;and a non-volatile memory for storing programmatic code which, whenexecuted by a processor, causes the pulse generator to generate thepulse stream in accordance with the plurality of stimulation parameters,wherein the plurality of stimulation parameters comprises a pulseamplitude having a range of 1 to 30 mAmp, wherein a value for the pulseamplitude is defined such that swallowing of the patient is not hinderedwhile the pulse stream is being delivered to the patient.
 2. The systemof claim 1, wherein the plurality of stimulation parameters furthercomprises a pulse width having a range of 5 μsec to 30 msec and whereina value for the pulse width is defined such that swallowing of thepatient is not hindered while the pulse stream is delivered to thepatient.
 3. The system of claim 1, further comprising an accelerometerconfigured to generate data indicative of when the patient is in asupine position.
 4. The system of claim 3, wherein the programmatic codecomprises a pre-programmed stimulation mode adapted to automaticallystimulate the LES during time periods in which the patient is in asupine position based on the data generated by the accelerometer.
 5. Thesystem of claim 4, wherein the automatic stimulation occurs after thepatient has been in the supine position for a predetermined period oftime and wherein the predetermined period of time is programmable and isin a range of 1 minute to 60 minutes.
 6. The system of claim 1, whereinthe pulse generator is adapted to be implanted.
 7. The system of claim1, wherein the system does not have a sensor to determine when thepatient is swallowing and does not modify the delivery of the pulsestream based on the swallowing.
 8. The system of claim 1, wherein theplurality of stimulation parameters comprises a pulse width having arange of 30 μsec to 5 msec, a pulse amplitude having a range of 2 to 15mAmp, and a pulse frequency having a range of 2 to 80 Hz.
 9. The systemof claim 1, wherein a portion of the system is adapted to be attached toan abdominal wall of the patient.
 10. The system of claim 1, wherein aportion of the system is adapted to be attached to an outer surface orserosa of a stomach wall of the patient.
 11. The system of claim 1,further comprising a housing, wherein the housing is adapted to containthe pulse generator and the non-volatile memory.
 12. The system of claim11, wherein the housing has dimensions greater than 6 mm and less than25 mm.
 13. The system of claim 11, wherein the at least one electrode isattached to the housing by insulated conductors.
 14. The system of claim13, wherein a length of the insulated conductors is no longer than 65cm.
 15. The system of claim 1, further comprising a rechargeable batteryin electrical communication with the pulse generator.
 16. The system ofclaim 1, wherein the at least one electrode is adapted to be positionedat least 1 mm from the patient's main vagal trunk and at least 1 mm fromthe patient's cardiac tissue.
 17. The system of claim 1, wherein, whenexecuted by a processor, said programmatic code further causes the pulsegenerator to generate the pulse stream 30 minutes before each meal. 18.The system of claim 1, wherein, when executed by a processor, saidprogrammatic code further causes the pulse generator to generate thepulse stream when the patient is in a supine position.
 19. The system ofclaim 1, wherein, when executed by a processor, said programmatic codefurther causes the pulse generator to generate the pulse stream prior toexpected gastroesophageal reflux diseases events.
 20. The system ofclaim 1, wherein, when executed by a processor, said programmatic codefurther causes the pulse generator to generate the pulse stream atequally spaced periods throughout a day.